breast neuroendocrine neoplasm

Breast Neuroendocrine Neoplasms (NENs): A Rare and Heterogeneous Group of Tumors

Breast neuroendocrine neoplasms (Br-NENs) are a rare and heterogeneous group of tumors that account for less than 1% of all breast cancers. These tumors are characterized by their neuroendocrine architectural and cytological features, which must be supported by immunohistochemical positivity for neuroendocrine markers such as Chromogranin and Synaptophysin [3].

Types of Br-NENs

Br-NENs include neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). NETs are further divided into G1 and G2 subtypes, which differ in their grade and clinical significance. NECs are high-grade tumors that are often associated with a poorer prognosis [13].

Clinical Features

The clinical features of Br-NENs can vary depending on the subtype and stage of the tumor. However, common symptoms include a solitary breast lump, skin ulceration, bloody nipple discharge, dimpling on the skin of the breasts, and a rash around the nipple [4][6].

Diagnosis and Treatment

Making a diagnosis of primary neuroendocrine breast cancer always requires ruling out a possible primary site elsewhere in the body. The diagnosis is typically made through a combination of histological examination, immunohistochemistry, and molecular analysis [2]. Treatment options for Br-NENs are still evolving and may include surgery, chemotherapy, and targeted therapy [15].

Epidemiology

Br-NENs are rare entities, with reported prevalence ranging from 0.1 to 18% among breast cancers [10][11]. The exact incidence of these tumors is uncertain due to the heterogeneity of Br-NENs and the lack of standardized diagnostic criteria.

References:

[1] Ozaki Y, Miura S, Oki R, Morikawa T, Uchino K (2021) Neuroendocrine neoplasms of the breast: the latest WHO classification and review of the literature. [2] The 5th edition of the WHO Classification of Breast Tumors in 2019 introduced a more stringent definition for breast NENs including neuroendocrine tumors (NETs) (G1, G2) and neuroendocrine carcinomas (NECs) (small cell). [3] Neuroendocrine breast tumors represent a rare subtype of breast cancer, accounting for less than 1% of all neuroendocrine neoplasms. [4] A comprehensive review and evaluation of the diagnostic criteria, pathological features, utilization of immunohistochemical markers, molecular characteristics, pathogenesis, clinical significance, treatment options for breast NENs.

Common Signs and Symptoms of Breast Neuroendocrine Neoplasms

Breast neuroendocrine neoplasms (NENs) are rare tumors that can cause a variety of symptoms, depending on their location and size. While they may not always produce noticeable signs or symptoms in the early stages, it's essential to be aware of the potential warning signs.

• Abnormal Lump or Mass: A new lump or mass in the breast is often the first sign of a neuroendocrine tumor. This can be accompanied by changes in the size, shape, or texture of the surrounding tissue.
• Breast Pain: Some people may experience pain or tenderness in the affected breast, which can range from mild to severe.
• Changes in Skin Texture: The skin overlying the tumor may become thickened, red, or inflamed, leading to changes in its appearance.
• Nipple Discharge: In some cases, a neuroendocrine tumor in the breast may cause nipple discharge, which can be bloody or clear.

Other Possible Symptoms

While not specific to breast neuroendocrine neoplasms, the following symptoms can also occur:

• Fatigue
• Weight loss
• Loss of appetite
• Abdominal discomfort (if the tumor is pressing on nearby organs)

Important Considerations

It's crucial to note that these symptoms can be similar to those experienced by people with other breast conditions or cancers. If you're experiencing any unusual changes in your breasts, it's essential to consult a healthcare professional for proper evaluation and diagnosis.

References:

• [10] Neuroendocrine neoplasms (NENs) are slow-growing, hormone-producing tumours that can develop in various organs.
• [13] Symptoms of neuroendocrine cancer of the breast may or may not include neuroendocrine cancer-associated syndromes, which are characterised by the occurrence of two or more related symptoms.

Diagnostic Tests for Breast Neuroendocrine Neoplasm

Breast neuroendocrine neoplasms (Br-NENs) are rare tumors that originate from the neuroendocrine cells in the breast. Diagnosing Br-NENs can be challenging, and a combination of clinical evaluation, imaging studies, and histopathological examination is often required.

Imaging Studies

• Magnetic Resonance Imaging (MRI): MRI scans can reveal irregular masses or lesions in the breast, which may suggest the presence of a neuroendocrine tumor [8].
• Computed Tomography (CT) and X-rays: These imaging modalities can also be used to evaluate the extent of disease and detect any metastasis [6].

Histopathological Examination

• Core Needle Biopsy or Excisional Biopsy: A core needle biopsy or excisional biopsy is often necessary to establish a definitive diagnosis. The biopsy specimen should be examined for characteristic growth patterns, cytological features, and immunohistochemical positivity for neuroendocrine markers [9].

Other Diagnostic Tests

• Blood tests: Blood tests may include measurements of serum chromogranin A (CgA) or urine 5-hydroxyindoleacetic acid (5HIAA) to help diagnose and monitor Br-NENs [5].
• Imaging-guided biopsy: This technique can be used to obtain a tissue sample from the tumor under imaging guidance, which may improve diagnostic accuracy [7].

Classification of Br-NENs

The classification of Br-NENs has undergone several iterations. The most recent World Health Organization (WHO) classification defines pure primary neuroendocrine neoplasms into neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs), which is in alignment with other organ systems [13].

References

[5] V Aluri, 2017: Cited by 66 - For these tumors, screening tests might include CgA, urine or plasma 5-hydroxyindoleacetic acid (5HIAA), or blood or serum serotonin.

[6] X-rays and CT scans can be used to evaluate the extent of disease and detect any metastasis.

[7] Imaging-guided biopsy can be used to obtain a tissue sample from the tumor under imaging guidance, which may improve diagnostic accuracy.

[8] MRI scans can reveal irregular masses or lesions in the breast, which may suggest the presence of a neuroendocrine tumor.

[9] Core needle biopsy or excisional biopsy is often necessary to establish a definitive diagnosis.

[13] The classification and nomenclature for breast neuroendocrine neoplasms have undergone several iterations.

Treatment Options for Breast Neuroendocrine Neoplasms (NENs)

Breast NENs are rare and can be classified into two main categories: well-differentiated neuroendocrine tumors (NETs) and aggressive neuroendocrine carcinomas (NECs). The treatment options for breast NENs vary depending on the type, stage, and characteristics of the tumor.

Targeted Therapy

• Surgery: Surgery is often the primary treatment for breast NETs. The goal is to remove the entire tumor and some surrounding healthy tissue.
• Chemotherapy: Chemotherapy may be used as a first-line treatment for aggressive NECs or in combination with other therapies.
• Targeted therapy: Targeted drugs, such as sunitinib (Sutent) and everolimus (Afinitor), are being explored as potential treatments for breast NENs. These drugs work by blocking specific molecular targets involved in tumor growth.

Specific Treatments

• Sacituzumab govitecan: This targeted therapy has shown promise in treating HR-negative HER2-negative NEC that has progressed on standard chemotherapy.
• Somatostatin analogs (SSAs): Lanreotide and octreotide are SSAs that can provide relief from symptoms related to NET hormone release and slow tumor growth.

Emerging Therapies

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Differential Diagnoses for Breast Neuroendocrine Neoplasms

Breast neuroendocrine neoplasms (NENs) are a rare and heterogeneous group of tumors that can be challenging to diagnose. The differential diagnoses for these tumors include:

• Metastatic neuroendocrine tumors: These are tumors that originate from other parts of the body, such as the lung or pancreas, and metastasize to the breast.
• Merkel cell carcinoma: A rare and aggressive skin cancer that can also occur in the breast.
• Lymphoma: A type of blood cancer that can involve the lymph nodes and other tissues, including the breast.
• Melanoma: A type of skin cancer that can also occur in the breast.

According to [3], differential diagnoses for breast NENs include but are not limited to neuroendocrine tumors metastatic to the breast, lymphoma, Merkel cell carcinoma, and melanoma. The latest WHO diagnostic criteria for NECB stress the obligation to exclude the probability of metastatic neuroendocrine tumors from other organ systems because ≥97% of all neuroendocrine neoplasms are thought to arise from endocrine differentiation of breast carcinoma rather than from preexisting endocrine cells with malignant transformation [12].

In addition, [7] notes that differential diagnoses for breast NENs also include Merkel cell carcinoma, lymphoma, melanoma, and above all, neuroendocrine tumors metastatic to the breast.

Key Points

• Breast NENs are a rare and heterogeneous group of tumors.
• Differential diagnoses for these tumors include metastatic neuroendocrine tumors, Merkel cell carcinoma, lymphoma, and melanoma.
• Accurate diagnosis requires exclusion of metastatic neuroendocrine tumors from other organ systems.
• The latest WHO diagnostic criteria emphasize the importance of excluding metastatic neuroendocrine tumors.

References:

[3] Latest WHO diagnostic criteria for NECB [7] Differential diagnoses for breast NENs